Kidney Cancer: The Basics

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What is the Kidney?

The kidneys are two bean-shaped organs that are located in the back of the abdomen, and that have many important functions essential for life. Among the most important are filtrating the blood, removing waste products from the blood and ensuring that the electrolytes within the blood are correctly balanced. The excess waste becomes urine. In addition, the kidneys produce erythropoietin, a hormone responsible for the production of oxygen carrying red blood cells, and a hormone called rennin, which helps control blood pressure.

Each of the kidneys can be divided into two main functional parts - the cortex and renal pelvis. The outer region of the kidney is called the cortex. The cortex consists of a series of tubes (called collecting tubules) and is responsible for the filtration of blood. The inner region of the kidney is called the renal pelvis. The renal pelvis contains medullary pyramids that collect the filtrate (urine) from collecting tubules in the cortex and send it through the ureters to the urinary bladder. Different types of cancers develop from the two different regions of the kidneys.

The kidneys are located in the back of the abdomen, directly in front of where the lowest ribs can be felt on a person's back. A physician can feel them in the abdomen at times, though often only if the kidney is enlarged or has a mass on it.

What is kidney cancer?

The definition of a tumor is a mass of abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any ability to spread to distant parts of the body. A tumor is called malignant, or cancer, if tumor cells are able to invade tissues and spread locally, as well as to distant parts of the body. Therefore, kidney cancer occurs when cells in either the cortex of the kidney, or cells in the renal pelvis, grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Renal cell carcinoma is the most common type of kidney cancer and accounts for about 9 out of 10 cases of kidney cancer. In renal cell cancer, malignant tumors can be growing in either one or both kidneys and there may be multiple tumors. There are several types of renal cell cancer. The type is determined by the appearance of the cancer cell under a microscope. Types of renal cell cancer include:

Papillary renal cell carcinoma - Accounts for about 1 out of 10 renal cell carcinomas. This type of cancer cell forms finger-like projections and when they absorb certain dyes they appear pink.

Chromophobe renal cell carcinoma - Accounts for about 5 out of 100 cases of renal cell carcinoma. They appear pale or clear but the cells are much larger than clear cell carcinoma.

Rare Types - These subtypes are rare and make up less than 1% of all occurrences of renal cell carcinoma. They include: collecting duct, multilocular cystic, medullary carcinoma, mucinous tubular and spindle cell carcinoma and neuroblastoma-associated renal cell carcinoma.

Unclassified - Very rare. They are determined to be unclassified when more than one type of cell exists or the cell does not fit into a specific category.

Transitional cell carcinomas, also known as urothelial carcinomas, account for about 5 to 10 out of every 100 diagnoses of kidney cancer. Transitional cell carcinoma is cancer in the lining of the renal pelvis where urine is stored before it enters the ureter to then travel to the bladder. This type of kidney cancer looks similar to bladder cancer cells when viewed under a microscope.

Wilms Tumor is a tumor commonly found in children and that is very rare in adults. It can affect either one or both kidneys and prior to being diagnosed the tumors are usually quite large.

Renal Sarcoma is a rare type of kidney cancer that begins in the blood vessels or connective tissue of the kidney and accounts for less than 1% of kidney cancers.

Benign kidney tumors are non-cancerous, but can grow very large and have an effect on the body. These include renal adenoma, oncocytoma and angiomyolipoma. They are treated using surgery, radiofrequency ablation and/or arterial embolization.

Am I at risk for kidney cancer?

The American Cancer Society estimates that in 2015 about 61,560 new cases of kidney cancer, inclusive of all types, will be diagnosed. It is estimated that there will be 14,080 deaths from kidney cancer in 2015. The average age of a person when diagnosed is 64 and kidney cancer is uncommon in people younger than 45. Kidney cancer is more common in men than women. African Americans and American Indians/Alaska Natives have slightly higher rates of renal cell carcinomas than do Caucasians.

Risks include:

Smoking - The most prominent risk is cigarette smoking. The increased risk is related to how much you smoke. Risk decreases when you stop smoking.

Obesity - Obesity changes different hormone levels, which can lead to kidney cancer.

Workplace Exposure - Exposure to cadmium, some herbicides and some organic solvents may increase risk of kidney cancer.

Family History - The risk for kidney cancer increases in persons with a first-degree relative who has had kidney cancer.

Other- Less commonly thought of factors include analgesic abuse, high blood pressure, and several uncommon hereditary diseases, including von Hippel-Lindau disease and polycystic kidney disease.

How can I prevent kidney cancer?

As cigarette smoking doubles the risk of kidney cancer, the best way to decrease your risk of developing kidney cancer is to quit smoking or never start. Maintain a healthy weight. Avoid toxins known to lead to cancer. The only other substantial risk factors for the development of kidney cancer are related to family history. The risk factor of having someone in the family with a history of kidney cancer, or rare genetic syndromes such as von Hippel Lindau and polycystic disease cannot be prevented. If you have this history, be sure your healthcare providers are aware.

What screening tests are available?

There are no screening tests for kidney cancer that are akin to mammography for breast cancer or colonoscopy for colorectal cancer. However, the use of CT scans and ultrasounds have enhanced the early detection of kidney cancer once signs or symptoms have developed (see below). Intravenous pyelograms (IVP) are used to assess kidney function. IVPs are done by injecting dye into a patient's arm and then taking x-rays of the abdomen to see that dye subsequently excreted by the kidneys as urine. Cytology is simply looking at urine under a microscope and looking for cancerous cells within the urine. Because they may cause early symptoms that lead to testing, kidney cancers that develop in the area of the collecting system may be detected earlier than those in other regions.

With the advent of CT scans and ultrasounds, 25-40% of kidney cancers are now detected incidentally during the work up of a different problem. These tumors are more likely to be smaller (hence causing no symptoms), and hence more likely to result in a cure.

What are signs of kidney cancer?

Kidney cancer presents as signs and symptoms of either the local tumor in the kidney or as signs and symptoms resulting from spread of disease to other locations in the body (metastatic disease). Symptoms resulting from local tumor growth include hematuria (blood in the urine), abdominal pain, and a flank mass. Hematuria, abdominal pain and a flank mass are the classic “triad” of symptoms of kidney cancer, though most patients will not have all three.

Hematuria is the most common symptom and presents as either gross hematuria, where the blood is visible in the urine, or as microscopic hematuria, where the blood is only detected by laboratory testing. Therefore, any presence of blood in the urine that is detected in a urine sample should be investigated.

Symptoms caused by metastatic disease include fever, weight loss, and night sweats (drenching sweats that require changing of clothes or bedsheets). Other symptoms include hypertension, increased calcium in the blood, and liver problems. These more unique symptoms are thought to be caused by chemical signals released by the tumor cells into the bloodstream and the body's reaction to them.

How is kidney cancer diagnosed and staged?

Diagnosis

Work up of a kidney cancer usually starts after the patient develops symptoms, with the exception of those cancers that are found incidentally. Tests done prior to treatment of kidney cancer are used to determine the extent of disease that is present so that treatment can be prescribed accordingly. This includes documenting the extent of disease both locally, in the tissues and lymph nodes surrounding the kidney, as well as ensuring there is no spread distantly, outside the area of the kidney (called metastases).

The most sensitive test to document local disease is the CT scan. MRI scans may be used to ensure the tumor has not involved any of the large blood vessels that are in the vicinity of the kidney. Other tests, including basic laboratory blood tests and analysis of the urine may be used to evaluate general health and the extent of the cancer. In addition, chest x-ray and bone scan may be done, to ensure that metastatic spread to the lungs and bones, respectively, has not occurred.

All of these tests are helpful, however, to confirm a diagnosis of any cancer, tissue or cells must be examined by a pathologist. Therefore, to obtain a diagnosis of kidney cancer, a biopsy is often done by inserting a needle into the presumed tumor mass. There are also times that the CT scan and/or MRI is so convincing that the mass is a tumor, that the initial biopsy is done during a surgical procedure, which is done to ultimately remove the kidney as treatment for the kidney cancer. The most appropriate surgical approach must be determined on an individual basis.

Staging

The results of these tests are put together to determine the stage of the cancer. The staging of a cancer documents the extent of disease and is often extremely important in terms of what treatment is offered to each individual patient. Before the staging systems are introduced, we will first describe some of the ways that cancers may grow and spread.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way kidney cancer can spread is by local extension to invade through the normal structures. This initially includes the kidney, hence causing hematuria, a mass, and abdominal pain. If more growth occurs, cancer can grow to involve the main vein that leaves the kidney (the renal vein), the large vein that returns blood from the bottom half of the body to the heart (the inferior vena cava), or into other organs-most commonly the adrenal glands which sit atop the kidneys.

Kidney cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Kidney cancer can spread, at times, into the lymph nodes surrounding the kidney, called the perirenal lymph nodes.

Kidney cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and cause distant metastases. Cancers of the kidney generally spread locally into the fat surrounding the kidney, the adrenal glands, or the veins prior to spreading via the lymphatic system or the bloodstream. However, tumors, especially larger tumors, can access the bloodstream and spread to the lungs and bones, most commonly. Kidney tumors have also been known to spread to the testis and ovaries through the testicular or ovarian veins that are in close proximity to the kidney.

The staging system used today in kidney cancer is designed to describe the extent of disease within the area of the kidney, in the surrounding lymph nodes, and distantly. This staging system is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the size of the "primary" tumor (the tumor in the kidney itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (metastases). The numbers 0-4 indicate increasing severity.

The "T" stage is as follows:

TX: The primary tumor cannot be assessed. T0: No evidence of a primary tumor.T1: The tumor is only in the kidney and is no larger than 7 centimeters. T1a: The tumor is 4 cm across or smaller and is only in the kidney.T1b: The tumor is larger than 4 cm but not larger than 7 cm across and is only in the kidney.T2: The tumor is larger than 7 cm across but is still only in the kidney.T2a: The tumor is more than 7 cm but not more than 10 cm across and is only in the kidney.T2b: The tumor is more than 10 cm across and is only in the kidney.T3: The tumor is growing into a major vein or into tissue around the kidney, but it is not growing into the adrenal gland (on top of the kidney) or beyond Gerota’s fascia (the fibrous layer that surrounds the kidney and nearby fatty tissue).T3a: The tumor is growing into the main vein leading out of the kidney (renal vein) or into fatty tissue around the kidney.T3b: The tumor is growing into the part of the large vein leading into the heart (vena cava) that is within the abdomen.T3c: The tumor has grown into the part of the vena cava that is within the chest or it is growing into the wall of the vena cava.T4: The tumor has spread beyond Gerota’s fascia and may have grown into the adrenal gland (on top of the kidney).

The "N" stage is as follows:

NX-Regional lymph nosed cannot be assessed.
N0-no spread to lymph nodes.
N1-tumor spread to a single or multiple lymph nodes.

The "M" stage is as follows:

M0-no tumor spread to other organs.
M1-tumor spread to other organs.

The overall stage is based on a combination of these T, N, and M parameters:

Stage I: T1N0M0

Stage II: T2N0M0

Stage III: T1N1M0, T2N1M0, T3N0M0 or T3N1M0

Stage IV: T4AnyNM0, AnyTAnyNM1

Though complicated, these staging systems help oncology providers determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer.

What are the treatments for kidney cancer?

Once your cancer is staged your care team will determine the best options for treatment. Your care team will be multidisciplinary; including providers from various specialties, such as a primary oncologist, urologist, radiation oncologist, pathologist, nutritionist, social worker and nurses. Your care team will take into consideration the stage of your disease, your overall health, possible side effects of treatment, probability of curing the disease and relief of symptoms when creating your care plan. Treatment options for kidney cancer include: surgery, radiation and chemotherapy. Less frequently used treatments include: ablation, active surveillance (monitoring the disease without active treatment), biologic therapy and targeted therapy. More than one treatment may be prescribed.

Treatment with Surgery

Surgery is the primary choice of treatment for kidney cancer. There are two types of surgical approaches associated with treatment of kidney cancer. A radical nephrectomy is the removal of the entire kidney, the adrenal gland that sits a top the kidney and the fatty tissue around the kidney. The removal of the kidney may be done through a large incision on the abdomen or back or may be done through a laparoscopic technique in which several small incisions are made rather than one large incision.

A second surgical treatment option is a nephron-sparing nephrectomy, also known as a partial nephrectomy. Only the part of the kidney affected by cancer is removed. It is the preferred treatment for early stage kidney cancer and is often used to remove T1a tumors and some T1b and T2a tumors. The benefit of a partial nephrectomy is to maintain as much kidney function as possible. A partial nephrectomy can be done through an open incision or through a laparoscopic procedure, the same as a radical nephrectomy. Each has benefits and risks associated, but the goal of these surgeries is good long-term renal function and cancer-free survival.

During both a radical and partial nephrectomy the surgeon may choose to perform a regional lymphadenectomy. In this procedure lymph nodes in the same region of the kidney are removed and checked for cancer cells. An adrenalectomy, removal of the adrenal gland, is always done in a radical nephrectomy but is performed during a partial nephrectomy at the surgeon’s discretion.

With any surgery, there are risks and side effects to take into consideration prior to making surgery part of the treatment plan. Possible side effects include: uncontrollable bleeding, blood clots, infections, pain, damage to surrounding organs, hernia, kidney failure, leakage of urine from the kidney, pneumothorax (unwanted air in the chest cavity, and reaction to anesthesia.

Radiation Therapy

Radiation is the use of high-energy x-rays to kill the tumor. This treatment is very complex and should be performed by a radiation team trained in this specialty. Radiation can be given by two different ways: external beam (from a machine outside the body) or brachytherapy (also called internal radiation, from an internally implanted radioactive source). Kidney cancer is not very sensitive to radiation but can be the treatment of choice for a patient who is not healthy enough to withstand surgery. Radiation can also be used to ease symptoms and side effects of kidney cancer including pain and bleeding. Side effects of radiation include skin changes at the site where the radiation is given, nausea, diarrhea and fatigue.

Chemotherapy

Chemotherapies are medications, given either orally or intravenously, that are used to kill tumor cells. Kidney cancer cells are often resistant to standard chemotherapy, so it is not considered a standard treatment for kidney cancer. If your care team decides that chemotherapy will be part of your treatment plan, you may be participating in a clinical trial.

Biologic Therapy (Immunotherapy)

Immunotherapy is the use of medications to enable the body’s immune system to fight and destroy cancer cells. The two immunotherapy medications primarily used to treat kidney cancer are interleukin-2 and interferon-alfa. Potential side effects of interleukin-2 include fatigue, hypotension (low blood pressure), difficulty breathing, heart attack, internal bleeding, fever and chills. Interferon is often used in conjunction with the targeted therapy agent bevacizumab (Avastin) and can cause fever, chills, muscle aches, fatigue and nausea.

Targeted Therapy

Targeted therapies are medications used to treat cancer that “target” a protein or receptor found on the cancer cell and interfere with the cell’s activity or growth. They may cause fewer, yet different, side effects than traditional chemotherapy. These therapies are typically used for metastatic disease, with the goal of shrinking the tumor, slowing the growth of the cancer, and giving patients periods of “stable” disease. Each targeted therapy “targets” a different receptor or cellular function (you can learn more about each therapy at the following links). Some of these medications include: sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab, pazopanib and axitinib.

The goal of your treatment plan will be to cure your kidney cancer or to slow the cancers growth while maintaining quality of life. Your oncology team will determine the best treatment plan based on the extent of the cancer, your health and available therapies.

Follow-up Care

Your follow-up care will be determined by your care team and will vary depending upon the type of treatment you received for your kidney cancer. If surgery was part of your treatment it is recommended that you have doctor visits, including a physical exam and blood work, every six months for the first two years and then yearly. A CT scan may be ordered three to six months after surgery to monitor for a recurrence of the cancer. Your care provider will determine a post treatment course that will vary if your cancer has been treated with a technique other than surgery. It is important to attend all of your appointments and to keep a list of any new side effects or symptoms you are experiencing.

After treatment, talk with your oncology team about receiving a survivorship care plan, which can help you manage the transition to survivorship and learn about long-term concerns and life after cancer. You can create your own survivorship care plan on OncoLink.